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John M Pettifor

Publications and source records attributed to John M Pettifor.

17 recordsLinked to original sources

Effect of ethnicity and sex on the growth of the axial and appendicular skeleton of children living in a developing country.

Bones in the axial and appendicular skeletons exhibit heterogeneous growth patterns between different ethnic and sex groups. However, the influence of this differential growth on the expression of bone mineral content is not yet established. The aims of the present study were to investigate: 1) whether there are ethnic and sex differences in axial and appendicular dimensions of South African children; and 2) whether regional segment length is a better predictor of bone mass than stature. Anthropometric measurements of stature, weight, sitting height, and limb lengths were taken on 368 black and white, male and female 9-year-old children. DXA (dual-energy x-ray absorptiometry) scans of the distal ulna, distal radius, and hip and lumbar spine were also obtained. Analyses of covariance were performed to assess differences in limb lengths, adjusted for differences in stature. Multiple regression analyses were used to assess significant predictors of site-specific bone mass. Stature-adjusted means of limb lengths show that black boys have longer legs and humeri but shorter trunks than white boys. In addition, black children have longer forearms than white children, and girls have longer thighs than boys. The regression analysis demonstrated that site-specific bone mass was more strongly associated with regional segment length than stature, but this had little effect on the overall pattern of ethnic and sex differences. In conclusion, there is a differential effect of ethnicity and sex on the growth of the axial and appendicular skeletons, and regional segment length is a better predictor of site-specific bone mass than stature.

Anthropometry↗

Early response to vitamin D2 in children with calcium deficiency rickets.

OBJECTIVE: To assess the effect of vitamin D(2) administration on serum vitamin D metabolite concentrations in calcium deficiency rickets. STUDY DESIGN: We administered vitamin D(2), 50,000 IU orally to 16 Nigerian children 15 to 48 months of age with radiographically active rickets. We measured calcium and vitamin D metabolites at baseline and at 1, 3, 7, and 14 days. RESULTS: At baseline, ranges of serum 25-hydroxyvitamin D (25(OH)D) concentrations were 18 to 40 nmol/L (7-16 ng/mL), and 1,25-dihydroxyvitamin D (1,25-(OH)(2)D) concentrations were 290 to 790 pmol/L (120-330 pg/mL). After vitamin D administration, serum 25(OH)D and 1,25(OH)(2)D concentrations rapidly rose and peaked at 2.8 and 1.9 times the baseline values (P < .001), respectively, at 3 days. Positive correlations between 1,25(OH)(2)D and 25(OH)D were strongest at day 3 (r = 0.84, P < .001) and weakest at day 14 (r = 0.41, P = .11). The relationship of 1,25(OH)(2)D with 25(OH)D at baseline and the increase in 1,25(OH)(2)D in response to vitamin D were similar to those described in children with vitamin D deficiency. However, unlike the pattern in vitamin D deficiency, 1,25(OH)(2)D remained positively correlated with 25(OH)D after administration of vitamin D. CONCLUSION: Dietary calcium deficiency increases the demand for 25(OH)D above that required in vitamin D deficiency to optimize 1,25(OH)(2)D concentrations. Assessment of vitamin D sufficiency in persons or communities may need to be adjusted for habitual dietary calcium intake.

Administration, Oral↗

Case-control study of breast milk calcium in mothers of children with and without nutritional rickets.

AIM: Despite similarly low calcium intakes and normal vitamin D status, only some Nigerian children develop nutritional rickets. We hypothesized that mothers with children who had developed rickets might have lower breast-milk calcium concentration than mothers with normal children and compared the breast-milk calcium concentration of mothers who had had children with rickets with those who had not (controls). METHODS: We collected breast milk from 35 Nigerian mothers who had previously had children with nutritional rickets. For each case mother, we collected breast milk from three matched control mothers at the same stage of lactation (+/-4 weeks) who had had no children with rickets. Data were collected about parity, stage of lactation, and the infant's intake. The mother's bone density was measured. RESULTS: The mean breast milk calcium concentration of mothers of children with rickets (4.30+/-1.24 mmol/L) was less than that of control mothers (4.65+/-1.03 mmol/L; P=0.034 in multivariate regression controlling for duration of lactation and resumption of menses). Forearm bone mineral content was significantly related to breast milk calcium concentration (r=0.20) after adjusting for height, weight, and bone area (P=0.028). CONCLUSION: Reduced breast-milk calcium concentration may contribute to a reduced calcium intake in infancy and predispose children to nutritional rickets.

Calcium↗

Nutritional rickets around the world: causes and future directions.

INTRODUCTION: Nutritional rickets has been described from at least 59 countries in the last 20 years. Its spectrum of causes differs in different regions of the world. METHODS: We conducted a systematic review of articles on nutritional rickets from various geographical regions published in the last 20 years. We extracted information about the prevalence and causes of rickets. RESULTS: Calcium deficiency is the major cause of rickets in Africa and some parts of tropical Asia, but is being recognised increasingly in other parts of the world. A resurgence of vitamin D deficiency has been observed in North America and Europe. Vitamin D-deficiency rickets usually presents in the 1st 18 months of life, whereas calcium deficiency typically presents after weaning and often after the 2nd year. Few studies of rickets in developing countries report values of 25(OH)D to permit distinguishing vitamin D from calcium deficiency. CONCLUSIONS: Rickets exists along a spectrum ranging from isolated vitamin D deficiency to isolated calcium deficiency. Along the spectrum, it is likely that relative deficiencies of calcium and vitamin D interact with genetic and/or environmental factors to stimulate the development of rickets. Vitamin D supplementation alone might not prevent or treat rickets in populations with limited calcium intake.

Africa↗

Rickets and vitamin D deficiency in children and adolescents.

This article discusses the pathogenesis, epidemiology, prevention, and treatment of nutritional rickets in children, highlighting the roles of exclusive breastfeeding and low dietary calcium intakes in its pathogenesis. The worldwide nature of the problem is described. Preventive strategies are discussed, and various treatment options are provided.

Adolescent↗

Stunting at 2 years in relation to body composition at 9 years in African urban children.

OBJECTIVE: To determine whether African urban children who were stunted at 2 years of age demonstrated an altered body composition by the end of childhood, before entering puberty, at 9 years of age. RESEARCH METHODS AND PROCEDURES: This was a mixed-longitudinal study of 330 prepubertal African children (182 boys) from Soweto-Johannesburg, South Africa. Anthropometric data at 2 years of age were compared with anthropometric, DXA-determined body composition and fat patterning in late childhood (7 to 9 years). RESULTS: Children who had been stunted at 2 years were significantly shorter and lighter than non-stunted children at 7 to 9 years, but there were no differences in their BMI or centralization of body fat. Previously stunted status significantly predicted reduced weight and height at 7 to 9 years but did not predict BMI, body composition, or fat patterning after controlling for potential confounding factors. The odds ratio for stunting at 2 years as a predictor of overweight at 7 to 9 years was not significant at 1.09 (95% confidence limits: 0.30, 3.98). DISCUSSION: Greater BMI in stunted infants does not demonstrate a tendency toward overweight or obesity but is a reflection of the greater reduction in height rather than weight in stunted children. Stunted children may be programmed to accumulate greater body fat at central sites during adolescence, but we have been unable to show that these changes are evident before the initiation of pubertal development.

Absorptiometry, Photon↗

Comparison of cross-sectional geometry of the proximal femur in white and black women from Detroit and Johannesburg.

UNLABELLED: There are known black-white differences in bone density measured by DXA but less is known about bone architecture. We compared cross-sectional geometric properties of the proximal femur in U.S. black (n = 86) and white (n = 151) and South African black (n = 60) and white (n = 48) postmenopausal women. Results are consistent with greater bone strength in the black groups in both countries. INTRODUCTION: There are well-known ethnic differences in bone density, but little is known about ethnic differences in bone architecture between U.S. and South African blacks and whites. MATERIALS AND METHODS: We compared bone density and cross-sectional geometric properties of the proximal femur in 237 U.S. black (n = 86) and white (n = 151) and 108 South African black (n = 60) and white (n = 48) postmenopausal women. The proximal femur (neck, intertrochanteric region, and proximal shaft regions of interest) was measured with DXA and further analyzed with a hip structural analysis program. For each region, BMD, cross-sectional area, outer diameter, section modulus, endosteal diameter, average cortical thickness, and the buckling ratio were estimated. RESULTS AND CONCLUSIONS: In the femoral neck, in both countries, the blacks had narrower endosteal diameters (mean difference, 2.6% and 5.1% in U.S. and South African women, respectively), thicker cortices (9.3% and 11.0%), and a lower buckling ratio (11.6% and 15.2%) despite a similar outer diameter. In the intertrochanteric region, the whites had a greater outer diameter (2.2% and 3.0% in U.S. and South African women, respectively), lower cross-sectional area (4.8% and 7.2%), and a higher buckling ratio (7.6% and 3.6%). There are fewer differences in the shaft. Compared with South African whites, U.S. whites had wider (mean difference 2.9%) femoral necks and a greater section modulus (6.4%) in the shaft. U.S. whites also had greater cross-sectional area in both the neck and shaft (5.2% and 4.6%, respectively). The U.S. blacks had significantly greater outer diameters, cross-sectional areas, endosteal diameters, and section moduli in the neck region compared with South African blacks. Our observations are consistent with greater bone strength in the black groups in both countries, and they also suggest that there are fewer differences between the same ethnic groups in the two countries than there are between different ethnic groups within a country.

Black or African American↗

Regression equations to estimate percentage body fat in African prepubertal children aged 9 y.

BACKGROUND: The regression equations of Slaughter and Dezenberg, which are based on mixed ethnic samples, are currently recommended for predicting body fat from skinfold-thickness measures in prepubescent children of African ancestry. These equations contain methodologic problems that could make them inappropriate for African children. OBJECTIVE: The objective was to apply the Slaughter and Dezenberg equations to predict body fat in African prepubertal children and to compare the results with body fat measured by dual-energy X-ray absorptiometry (DXA). If significantly different outcomes were observed, then the objective was to develop new prediction equations and validate them on African children. DESIGN: The Slaughter and Dezenberg equations were applied to a cross-sectional sample of 214 prepubescent (Tanner stage 1) African children (118 boys). Body fat was determined by DXA, and subcutaneous fat at triceps, biceps, subscapular, suprailiac, thigh, and calf sites was measured with use of Holtain calipers. A randomly selected sample of 134 participants (78 boys) was used to generate new prediction equations that were validated on the remaining 80 participants (40 boys). RESULTS: The Slaughter and Dezenberg equations significantly underestimated (P < 0.001) body fat compared with DXA in both boys and girls. The best combination of skinfold thicknesses to predict body fat in African prepubertal boys, controlling for chronologic age, was triceps, biceps, subscapular, suprailiac, and thigh (SEE = 2.87), and for girls it was biceps, subscapular, suprailiac, thigh, and calf (SEE = 3.51). CONCLUSION: The Slaughter and Dezenberg equations are unsuitable for predicting body fat in 9-y-old African prepubertal children. New equations that are based on skinfold-thickness combinations from African children provide more accurate estimates.

Absorptiometry, Photon↗

Calcium absorption in Nigerian children with rickets.

BACKGROUND: Nutritional rickets is common in Nigerian children and responds to calcium supplementation. Low dietary calcium intakes are also common in Nigerian children with and without rickets. OBJECTIVE: The objective was to assess intestinal calcium absorption in Nigerian children with rickets. DESIGN: Calcium absorption was assessed in 15 children with active rickets (2-8 y of age) and in 15 age- and sex-matched children without rickets by using a dual-tracer stable-isotope method. The children with rickets were supplemented with calcium for 6 mo; calcium absorption was reevaluated 12 mo after the baseline study. Fractional calcium absorption could be determined in 10 children with rickets and in 10 children without rickets. RESULTS: The children with and without rickets had dietary calcium intakes of approximately 200 mg/d. Compared with the control children, the children with rickets had lower serum 25-hydroxyvitamin D and calcium concentrations and greater 1,25-dihydroxyvitamin D and parathyroid hormone concentrations. In fact, there were 15 rachitic and 15 control children in the study. Mean (+/-SD) fractional calcium absorption did not differ between those with (61 +/- 20%) and without (63 +/- 13%) rickets (P = 0.47). Calcium absorption was not associated with serum concentrations of calcium, alkaline phosphatase, 25-hydroxyvitamin D, 1,25-dihydroxyvitamin D, or parathyroid hormone. Mean fractional calcium absorption was significantly greater after (81 +/- 10%) than before (61 +/- 20%) calcium supplementation for the treatment of rickets (P = 0.035). CONCLUSIONS: In Nigerian children with rickets, the capacity to absorb calcium is not impaired; however, fractional calcium absorption increases after the resolution of active disease. Calcium absorption may be inadequate to meet the skeletal demands of children with rickets during the active phase of the disease, despite being similar to that of control children.

Calcium↗

Nutritional rickets: deficiency of vitamin D, calcium, or both?

Nutritional rickets remains a public health problem in many countries, despite dramatic declines in the prevalence of the condition in many developed countries since the discoveries of vitamin D and the role of ultraviolet light in prevention. The disease continues to be problematic among infants in many communities, especially among infants who are exclusively breast-fed, infants and children of dark-skinned immigrants living in temperate climates, infants and their mothers in the Middle East, and infants and children in many developing countries in the tropics and subtropics, such as Nigeria, Ethiopia, Yemen, and Bangladesh. Vitamin D deficiency remains the major cause of rickets among young infants in most countries, because breast milk is low in vitamin D and its metabolites and social and religious customs and/or climatic conditions often prevent adequate ultraviolet light exposure. In sunny countries such as Nigeria, South Africa, and Bangladesh, such factors do not apply. Studies indicated that the disease occurs among older toddlers and children and probably is attributable to low dietary calcium intakes, which are characteristic of cereal-based diets with limited variety and little access to dairy products. In such situations, calcium supplements alone result in healing of the bone disease. Studies among Asian children and African American toddlers suggested that low dietary calcium intakes result in increased catabolism of vitamin D and the development of vitamin D deficiency and rickets. Dietary calcium deficiency and vitamin D deficiency represent 2 ends of the spectrum for the pathogenesis of nutritional rickets, with a combination of the 2 in the middle.

Calcium↗

Nutritional rickets in ichthyosis and response to calcipotriene.

Nutritional rickets has occasionally been described in children with lamellar ichthyosis, but their vitamin D endocrine status has not been described. We report 3 cases of vitamin D-deficiency rickets associated with ichthyosis in African children. A 13-month-old Nigerian boy with lamellar ichthyosis had rib beading, elevated alkaline phosphatase, and rachitic changes on radiographs. His rickets did not resolve with calcium therapy, and his 25-hydroxyvitamin D level was low. His rickets resolved with parenteral vitamin D treatment, but his skin did not improve. Topical 0.005% calcipotriene (an analog of 1,25-dihydroxyvitamin D that has been useful in treating adults with psoriasis) was similarly ineffective in improving the child's skin condition. An 8-year-old Nigerian boy with life-long skin findings consistent with lamellar ichthyosis had windswept deformity of the legs with rib beading and enlargement of the wrists and ankles. Radiographs showed active rickets, and the boy had an elevated alkaline phosphatase level and a decreased calcium level. Before knowing that his 25-hydroxyvitamin D level was low, he was treated with calcium and showed radiologic improvement. The skin did not improve with resolution of the rickets but did improve with unilateral topical application of 0.005% calcipotriene. A 7-year-old South African girl presented with progressive windswept deformities of the legs and a 4-year history of skin disease (and a skin biopsy consistent with X-linked ichthyosis). Radiographs and biochemical data confirmed active rickets. Her rickets improved dramatically with vitamin D treatment. Thus, 3 African children with ichthyosis developed vitamin D-deficiency rickets, probably because of a combination of impaired skin production and sunlight avoidance. This is consistent with previous findings of hypovitaminosis D in adults with ichthyosis and other disorders of keratinization. Measurement of 25-hydroxyvitamin D may be indicated in children with ichthyosis to identify those at risk for vitamin D-deficiency rickets, because it is possible that the cutaneous synthesis of vitamin D in such children is impaired. Although the ichthyosis did not improve with resolution of vitamin D deficiency and rickets, 1 of 2 children treated with topical calcipotriene showed improvement in the treated areas of skin. Calcipotriene does not seem to be effective in reversing systemic vitamin D deficiency but can be effective in improving the severity of skin disease in children with ichthyosis.

Administration, Cutaneous↗

Vitamin D metabolism in a frugivorous nocturnal mammal, the Egyptian fruit bat (Rousettus aegyptiacus).

The nocturnal, frugivorous Egyptian fruit bat (Rousettus aegyptiacus) has no obvious access to either endogenous or dietary sources of vitamin D. We hypothesized that this species under natural conditions would be vitamin D deficient and that both serum mineral concentrations and vitamin D metabolite concentrations would be low. Both wild populations and captive populations appear to have an impoverished vitamin D status, as concentrations of the principle circulating metabolite, 25-hydroxyvitamin D [25(OH)D] are undetectable (<4 ng/mL) and those of the active metabolite, 1,25-dihydroxyvitamin D [1,25(OH)(2)D] are low. Intraperitoneal administration of labelled 25(OH)D revealed enhanced 1 alpha-hydroxylase activity confirming a natural state of vitamin D deficiency. This may account for the undetectable levels of 25(OH)D; for limited amounts of the prohormone substrate are rapidly converted to the active hormone. Both vitamin D(2) and D(3) metabolites were detected in bat serum, albeit in very small amounts, inferring that in their natural habitat fruit bats may have limited access to both exogenous dietary sources and endogenous sources. Despite the low levels of vitamin D metabolites in wild-caught and captive D-unsupplemented individuals, serum mineral concentrations were well regulated and similar to those of bats receiving D-supplements, with no pathological problems associated with vitamin D deficiency evident.

Alkaline Phosphatase↗

Rickets.

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Calcium↗

The usefulness of clinical features to identify active rickets.

To develop a clinical prediction rule that could accurately identify children with active rickets in countries where nutritional rickets is common, we prospectively recorded clinical features in 736 Nigerian children aged 18 months and older presenting with leg deformities or inability to walk. We scored radiographs of the wrists and knees for active rickets of the growth plates. Sensitivities and specificities of clinical variables for radiographically active rickets were calculated and, using logistic regression, we derived a clinical prediction rule. The prediction rule was tested in a validation set of 89 children. Wrists and costochondral enlargement were the clinical signs with the best combination of sensitivity (72% and 76%, respectively) and specificity (81% and 64%, respectively) for active rickets. Age < 5 years, height-for-age Z-score < -2, leg pain during walking, wrist enlargement and costochondral enlargement were independently predictive of active rickets (p < 0.01 for each in multivariate model). In the validation set, any three of these clinical features accurately identified 87% of children with active rickets, whereas only 24% of those without active rickets had three or more features. We conclude that clinical features can be used to identify children with active rickets.

Age Factors↗

The discriminative value of C-reactive protein levels in distinguishing between community-acquired bacteraemic and respiratory virus-associated lower respiratory tract infections in HIV-1-infected and -uninfected children.

This study assessed the value of routine CRP measurements to discriminate between bacterial and viral lower respiratory tract infection (LRTI) in HIV-1-infected and -uninfected children. A total of 570 children, prospectively enrolled, were categorised into four aetiological groups, as follows: (i) bacteraemic pneumonia (n = 50), (ii) respiratory virus-associated LRTI (n = 146), (iii) bacteraemic and respiratory virus-associated (mixed) LRTI (n = 10), and (iv) LRTI of undetermined aetiology (n = 364). The discriminative ability of threshold CRP values was evaluated, and values predicting bacteraemic pneumonia were used to construct receiver-operating characteristic (ROC) plots. Median CRP values were significantly higher in bacteraemic pneumonia (195 mg/L, p < 0.0001), and threshold CRP values ranging from 10 to 100 mg/L differentiated bacteraemic from virus-associated LRTI (p < 0.0001). The discriminative ability of CRP values assessed by ROC plots in pneumonia is 80%, and CRP > or = 10 mg/L identified 90% of all bacteraemic pneumonia. In HIV-1 infection, median CRP values were significantly higher in bacteraemic pneumonia (200 mg/L) but correlated with levels in uninfected children, irrespective of LRTI aetiology. Although CRP responses are significantly different in bacteraemic and virus-associated LRTI, the considerable overlap between these aetiological groups hinders selection of threshold CRP values that are clinically useful in differentiating bacteraemic from virus-associated LRTI pneumonia.

AIDS-Related Opportunistic Infections↗